Apolipoprotein E Mediates Enhanced Plasma High-Density Lipoprotein Cholesterol Clearance by Low-Dose Streptococcal Serum Opacity Factor via Hepatic Low-Density Lipoprotein Receptors In Vivo
Objective—Recombinant streptococcal serum opacity factor (rSOF) mediates the in vitro disassembly of human plasma high-density lipoprotein (HDL) into lipid-free apolipoprotein (apo) A-I, a neo-HDL that is cholesterol poor, and a cholesteryl ester–rich microemulsion (CERM) containing apoE. Given the occurrence of apoE on the CERM, we tested the hypothesis that rSOF injection into mice would reduce total plasma cholesterol clearance via apoE-dependent hepatic low-density lipoprotein receptors (LDLR).
Methods and Results—rSOF (4 μg) injection into wild-type C57BL/6J mice formed neo-HDL, CERM, and lipid-free apoA-I, as observed in vitro, and reduced plasma total cholesterol (−43%, t1/2=44±18 minutes) whereas control saline injections had a negligible effect. Similar experiments with apoE−/− and LDLR−/− mice reduced plasma total cholesterol ≈0% and 20%, respectively. rSOF was potent; injection of 0.18 μg of rSOF produced 50% of maximum reduction of plasma cholesterol 3 hours postinjection, corresponding to a ≈0.5-mg human dose. Most cholesterol was cleared hepatically (>99%), with rSOF treatment increasing clearance by 65%.
Conclusion—rSOF injection into mice formed a CERM that was cleared via hepatic LDLR that recognize apoE. This reaction could provide an alternative mechanism for reverse cholesterol transport.
- Received August 19, 2010.
- Accepted April 22, 2011.
- © 2011 American Heart Association, Inc.